Gardasil

Last updated

Gardasil
Gardasil vaccine and box new.jpg
Gardasil quadrivalent HPV [types 6, 11, 16, 18]
Vaccine description
TargetFor Gardasil 9: Human papillomavirus, Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
Vaccine type Protein subunit
Clinical data
Trade names Gardasil, Gardisil, Silgard, others
AHFS/Drugs.com Monograph
MedlinePlus a607016
License data
Pregnancy
category
Routes of
administration 		Intramuscular injection
ATC code
Legal status
Legal status
Identifiers
PubChem SID
DrugBank
ChemSpider
  • none
UNII
KEGG
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Gardasil is an HPV vaccine for use in the prevention of certain strains of human papillomavirus (HPV). [10] [7] [8] [9] [11] It was developed by Merck & Co. [12] High-risk human papilloma virus (hr-HPV) genital infection is the most common sexually transmitted infection among women. [13] The HPV strains that Gardasil protects against are sexually transmitted, [14] specifically HPV types 6, 11, 16 and 18. [15] [16] HPV types 16 and 18 cause an estimated 70% of cervical cancers, [17] [18] and are responsible for most HPV-induced anal, [19] vulvar, vaginal, [20] and penile cancer cases. [19] HPV types 6 and 11 cause an estimated 90% of genital warts cases. [21] HPV type 16 is responsible for almost 90% of HPV-positive oropharyngeal cancers, [22] and the prevalence is higher in males than females. [22] Though Gardasil does not treat existing infection, vaccination is still recommended for HPV-positive individuals, as it may protect against one or more different strains of the disease. [23]

Contents

The vaccine was approved for medical use in the United States in 2006, [24] [25] initially for use in females aged 9–26. [26] In 2007, the Advisory Committee on Immunization Practices recommended Gardasil for routine vaccination of girls aged 11 and 12 years. [27] As of August 2009, vaccination was recommended for both males and females before adolescence and the beginning of potential sexual activity. [15] [6] [28] By 2011, the vaccine had been approved in 120 other countries. [29]

In 2014, the US Food and Drug Administration (FDA) approved a nine-valent version, Gardasil 9, to protect against infection with the strains covered by the first generation of Gardasil as well as five other HPV strains responsible for 20% of cervical cancers (types 31, 33, 45, 52, and 58). [6] [30] [31] In 2018, the FDA approved expanded use of Gardasil 9 for individuals 27 to 45 years old. [32]

Types

Gardasil is available as Gardasil which protects against 4 types of HPV (6, 11, 16, 18) and Gardasil 9 which protects against an additional 5 types (31, 33, 45, 52, 58). [5] [6] [8] [9] [33]

Medical uses

In the United States, Gardasil is indicated for: [34]

In the European Union, Gardasil is indicated for active immunization of individuals from the age of nine years against the following HPV diseases: [8]

Gardasil is a vaccine to prevent HPV, that, for maximum effect, is recommended for individuals prior to them becoming sexually active. [23] Moreover, evidence supports the conclusion that women who were already infected with one or more of the four HPV types targeted by the vaccine (HPV types 6, 11, 16, or 18) were protected from clinical disease caused by the remaining HPV types in the vaccine. [23] [ failed verification ] HPV types 16 and 18 cause an estimated 70% of cervical cancers, [17] [18] and are responsible for most HPV-induced anal cancers. [19] Gardasil also protects against vulvar and vaginal cancers caused by HPV types 16 and 18, [20] as well as most penile cancers caused by these two HPV types. [35]

In addition, protection against HPV types 6 and 11 may eliminate up to 90% of the cases of genital warts. [21] Common plantar warts—e.g., caused by HPV types 1, 2, and 4 [36] —are not prevented by this vaccine.

In 2010, Gardasil was approved by the FDA for prevention of anal cancer and associated precancerous lesions due to HPV types 6, 11, 16, and 18 in people aged 9 through 26 years. [37]

HPV infections, especially HPV 16, contribute to some head and neck cancer (HPV is found in an estimated 26–35% of head and neck squamous cell carcinoma). [38] [39] In principle, HPV vaccines may help reduce incidence of such cancers caused by HPV, but this has not been demonstrated. [40] [ needs update ] In June 2020, the FDA approved the use of Gardasil for the prevention of head and neck cancers. [41] [42]

The FDA approved Gardasil 9 for women and men aged 27 to 45 based on the vaccine being 88% effective against persistent HPV infections that cause certain types genital warts and cancers in females. Vaccine efficacy in males in this age group was inferred. [32]

Efficacy

A 2020 longitudinal study tracking over 1.6 million Swedish girls and women over an eleven-year period found half as many cervical cancer cases in all women who had been vaccinated, and amongst women who had been vaccinated before the age of 17 a 78% reduction in cervical cancer, "a substantially reduced risk of invasive cervical cancer at the population level." [43]

An alternative vaccine known as Cervarix protects against two oncogenic strains of HPV, 16 and 18. [44]

The National Cancer Institute says, "To date, protection against the targeted HPV types has been found to last for at least 10 years with Gardasil, at least 9 years with Cervarix, and at least 6 years with Gardasil 9. Long-term studies of vaccine efficacy that are still in progress will help scientists better understand the total duration of protection." [45]

Gardasil has been shown to be partially effective (approximately 38%) in preventing cervical cancer caused by ten other high-risk HPV types. [46]

Antibody levels at month 3 (one month post-dose number two) are substantially higher than at month 24 (18 months post-dose number three), suggesting that protection is achieved by month 3 and perhaps earlier. [6] In 2014, the World Health Organization (WHO) recommended that countries offer the vaccine in a two dose schedule to girls aged under 15, with each dose at least six months apart. [21] [47] The United Kingdom, Switzerland, Mexico, and Quebec province of Canada are among the countries or territories that have implemented this as of June 2015. The CDC recommended the vaccines be delivered in two shots over six months. [48]

Males

Gardasil is also effective in males, providing protection against genital warts, anal warts, anal cancer, and some potentially precancerous lesions caused by some HPV types. [16] [49] [50] Gardasil vaccine has been shown to decrease the risk of young men contracting genital warts. [51] In the United States, the FDA approved administration of the Gardasil vaccine to males between ages 9 and 26 in 2009. [52] [53] The FDA approved administration of the Gardasil 9 vaccine to males between ages 9 and 15 in 2014, and extended the age indication, by including males between ages 16 and 26, in 2015. [54] [55] [56] In the UK, HPV vaccines are licensed for males aged 9 to 15 and for females aged 9 to 26. [57]

Men who have sex with men (MSM) are particularly at risk for conditions associated with HPV types 6, 11, 16, and 18; diseases and cancers that have a higher incidence among MSM include anal intraepithelial neoplasias, anal cancers, and genital warts. HPV type 16 is also responsible for almost 90% of HPV-positive oropharyngeal squamous-cell carcinoma (OPSCC), [22] a form of cancer that affects the mouth, tonsils, and throat; [22] [58] the prevalence of HPV-positive oropharyngeal cancers is higher in males than females. [22] A 2005 study found that 95% of HIV-infected gay men also had anal HPV infection, of whom 50% had precancerous HPV-caused lesions. [59]

Administration

Gardasil is given in three injections over six months. The second injection is two months after the first, and the third injection is six months after the first shot was administered. [15] [6] Alternatively, in some countries it is given as two injections with at least six months between them, for individuals aged 9 years up to and including 13 years. [4] [60]

Adverse effects

As of April 2014, more than 170 million doses of Gardasil had been distributed worldwide. [61] The vaccine was tested in thousands of females (ages 9 to 26). [62] The US Food and Drug Administration (FDA) and the US Centers for Disease Control and Prevention (CDC) consider the vaccine to be safe. It does not contain mercury, thiomersal, live viruses or dead viruses, but virus-like particles, which cannot reproduce in the human body. [62]

The vaccine has mostly minor side effects, such as pain around the injection area. [62] Fainting is more common among adolescents receiving the Gardasil vaccine than in other kinds of vaccinations. Patients should remain seated for 15 minutes after they receive the HPV vaccine. [6] There have been reports that the shot is more painful than other common vaccines, and the manufacturer Merck partly attributes this to the virus-like particles within the vaccine. [63] General side effects of the shot may include joint and muscle pain, fatigue, physical weakness and general malaise. [6] [64]

The FDA and the CDC said that with millions of vaccinations "by chance alone some serious adverse effects and deaths" will occur in the time period following vaccination, but they have nothing to do with the vaccine. [65] More than twenty women who received the Gardasil vaccine have died, but these deaths have not been causally connected to the shot, as correlation does not imply causation. [65] Where information has been available, the cause of death was explained by other factors. [66] [67] Likewise, a small number of cases of Guillain–Barré syndrome (GBS) have been reported following vaccination with Gardasil, though there is no evidence linking GBS to the vaccine. [28] [68] [69] It is unknown why a person develops GBS, or what initiates the disease. [70]

The FDA and the CDC monitor events to see if there are patterns, or more serious events than would be expected from chance alone. [66] The majority (68%) of side effects data were reported by the manufacturer, but in about 90% of the manufacturer reported events, no follow-up information was given that would be useful to investigate the event further. [71] In February 2009, the Spanish Ministry of Health suspended use of one batch of Gardasil after health authorities in the Valencia region reported that two girls had become ill after receiving the injection. Merck has stated that there was no evidence Gardasil was responsible for the two illnesses. [72]

Ingredients

The following are the ingredients found in the different formulations of HPV vaccines: [73]

Biotechnology

The HPV major capsid protein, L1, can spontaneously self-assemble into virus-like particles (VLPs) that resemble authentic HPV virions. Gardasil contains recombinant VLPs assembled from the L1 proteins of HPV types 6, 11, 16 and 18. Since VLPs lack the viral DNA, they cannot induce cancer. They do, however, trigger an antibody response that protects vaccine recipients from becoming infected with the HPV types represented in the vaccine. The L1 proteins are produced by separate fermentations in recombinant Saccharomyces cerevisiae and self-assembled into VLPs. [74]

Public health

The National Cancer Institute writes:

Widespread HPV vaccination has the potential to reduce cervical cancer incidence around the world by as much as 90%. In addition, the vaccines may reduce the need for screening and subsequent medical care, biopsies, and invasive procedures associated with follow-up from abnormal cervical screening, thus helping to reduce health care costs and anxieties related to follow-up procedures. [45]

Long-term impact and cost-effectiveness

Whether the effects are temporary or lifelong, widespread vaccination could have a substantial public health impact. As of 2018, studies have proven that cervical cancer rates have dropped significantly since the introduction of Gardasil. [75] Before Gardasil was introduced in 2006, 270,000 women died of cervical cancer worldwide in 2002. [76] As of 2014, the mortality rate from cervical cancer has dropped 50% from 1975 which is due to the Gardasil vaccination along with increased focus on cervical screening. [77] Acting FDA administrator Andrew von Eschenbach said the vaccine will have "a dramatic effect" on the health of women around the world. [78] Gardasil is an important tool in reducing cervical cancer rates even in countries where screening programs are routine. The National Cancer Institute estimated that 9,700 women would develop cervical cancer in 2006, and 3,700 would die. [79]

Merck and CSL Limited are expected[ needs update ] to market Gardasil as a cancer vaccine, rather than an STD vaccine. In the early years of Gardasil's introduction it was unclear how widespread the use of the three-shot series would be, in part because of its $525 list price ($175 each for three shots). [80] But as of 2013, vaccine coverage has been rising. [75] In 2013, about 55% of girls ages 13–17 years had at least one dose of the vaccination covered, up from 29% in 2007. Coverage for women ages 18–34 also has increased significantly since 2007. [75]

Studies using different pharmacoeconomic models predict that vaccinating young women with Gardasil in combination with screening programs may be more cost effective than screening alone. [81] These results have been important in decisions by many countries to start vaccination programs. [82] For example, the Canadian government approved $300 million to buy the HPV vaccine in 2008 after deciding from studies that the vaccine would be cost-effective especially by immunizing young women. [83] Marc Steben, an investigator for the vaccine, wrote that the financial burden of HPV related cancers on the Canadian people was already $300 million per year in 2005, so the vaccine could reduce this burden and be cost-effective. [84]

Since penile and anal cancers are much less common than cervical cancer, HPV vaccination of young men is likely to be much less cost-effective than for young women yet is still recommended due to the existent risk (including oral cancer). [65]

The August 2009 issue of the Journal of the American Medical Association had an article reiterating the safety of Gardasil [68] and another questioning the way it was presented to doctors and parents.

The new vaccine against 4 types of human papillomavirus (HPV), Gardasil, like other immunizations appears to be a cost-effective intervention with the potential to enhance both adolescent health and the quality of their adult lives. However, the messages and the methods by which the vaccine was marketed present important challenges to physician practice and medical professionalism. By making the vaccine's target disease cervical cancer, the sexual transmission of HPV was minimized, the threat of cervical cancer to adolescents was maximized, and the subpopulations most at risk practically ignored. The vaccine manufacturer also provided educational grants to professional medical associations (PMAs) concerned with adolescent and women's health and oncology. The funding encouraged many PMAs to create educational programs and product-specific speakers' bureaus to promote vaccine use. However, much of the material did not address the full complexity of the issues surrounding the vaccine and did not provide balanced recommendations on risks and benefits. As important and appropriate as it is for PMAs to advocate for vaccination as a public good, their recommendations must be consistent with appropriate and cost-effective use. [85]

According to the CDC, as of 2012, use of the HPV vaccine had cut rates of infection with HPV-6, -11, -16 and -18 in half in American teenagers (from 11.5% to 4.3%) and by one third in American women in their early twenties (from 18.5% to 12.1%). [86]

History

Research findings that pioneered the development of the vaccine began in 1991 by investigators Jian Zhou and Ian Frazer in The University of Queensland, Australia. Researchers at UQ found a way to form non-infectious virus-like particles (VLP), which could also strongly activate the immune system. Subsequently, the vaccine was developed in parallel by researchers at Georgetown University Medical Center, the University of Rochester, the University of Queensland in Australia, and the US National Cancer Institute. [87] MedImmune, GSK, and Merck & Co. advanced these technologies and conducted clinical trials. [88]

In December 2014, the FDA approved Gardasil 9, which protects against nine strains of HPV. [89] [90]

Society and culture

United States

A few conservative groups, such as the Family Research Council (FRC), have expressed their fears that vaccination with Gardasil might give girls a false sense of security regarding sex and lead to promiscuity, [78] [91] [92] [93] but no evidence exists to suggest that girls who were vaccinated went on to engage in more sexual activity than unvaccinated girls. [94] Merck, the manufacturer of the vaccine, has lobbied that state governments make vaccination with Gardasil mandatory for school attendance, [95] which has upset some conservative and libertarian groups. [78] [96] [91]

The governor of Texas, Rick Perry, issued an executive order adding Gardasil to the state's required vaccination list, which was later overturned by the Texas legislature. Even though Perry also allowed parents to opt out of the program more easily, Perry's order was criticized, by fellow presidential candidates Rick Santorum and Michele Bachmann during the 2012 Republican Party presidential debate as being an overreach of state power in a decision properly left to parents. [97]

Japan

In June 2013, the Japanese government issued a notice that "cervical cancer vaccinations should no longer be recommended for girls aged 12 to 16" while an investigation is conducted into certain adverse events including pain and numbness in 38 girls. [98] The vaccines sold in Japan are Cervarix, made by GSK plc (formerly GlaxoSmithKline) of the United Kingdom, and Gardasil, made by Merck Sharp & Dohme. An estimated 3.28 million people have received the vaccination; 1,968 cases of possible side effects have been reported. [99] In January 2014, the Vaccine Adverse Reactions Review Committee concluded that there was no evidence to suggest a causal association between the HPV vaccine and the reported adverse events, but did not reinstate proactive recommendations for its use. [100] A study on girls in Sapporo showed that since the Japanese government's suspension of recommending the vaccine, completion rates for the full course of vaccination have dropped to 0.6%. [100] On 26 November 2021, the Ministry of Health, Labour, and Welfare of Japan officially issued an announcement to resume active recommendations of the HPV vaccine after 8.5 years of suspension and municipalities are expected to restart such active recommendations from April 2022. [101]

Related Research Articles

<span class="mw-page-title-main">Wart</span> Small, rough growth resembling a cauliflower or a solid blister

Warts are non-cancerous viral growths usually occurring on the hands and feet but which can also affect other locations, such as the genitals or face. One or many warts may appear. They are distinguished from cancerous tumors as they are caused by a viral infection, such as a human papillomavirus, rather than a cancer growth.

<span class="mw-page-title-main">Cervical cancer</span> Cancer arising from the cervix

Cervical cancer is a cancer arising from the cervix or in the any layer of the wall of the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal vaginal bleeding, pelvic pain or pain during sexual intercourse. While bleeding after sex may not be serious, it may also indicate the presence of cervical cancer.

<span class="mw-page-title-main">Human papillomavirus infection</span> Human disease

Human papillomavirus infection is caused by a DNA virus from the Papillomaviridae family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and results in either warts or precancerous lesions. These lesions, depending on the site affected, increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, tonsils, or throat. Nearly all cervical cancer is due to HPV, and two strains – HPV16 and HPV18 – account for 70% of all cases. HPV16 is responsible for almost 90% of HPV-positive oropharyngeal cancers. Between 60% and 90% of the other cancers listed above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis.

<span class="mw-page-title-main">Genital wart</span> Sexually transmitted infection caused by certain types of human papillomaviruses

Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV). They may be flat or project out from the surface of the skin, and their color may vary; brownish, white, pale yellow, pinkish-red, or gray. There may be a few individual warts or several, either in a cluster or merged together to look cauliflower-shaped. They can be itchy and feel burning. Usually they cause few symptoms, but can occasionally be painful. Typically they appear one to eight months following exposure. Warts are the most easily recognized symptom of genital HPV infection.

<span class="mw-page-title-main">Plantar wart</span> Medical condition

A plantar wart is a wart occurring on the bottom of the foot or toes. Its color is typically similar to that of the skin. Small black dots often occur on the surface. One or more may occur in an area. They may result in pain with pressure such that walking is difficult.

<span class="mw-page-title-main">Anal cancer</span> Medical condition

Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. Symptoms may include bleeding from the anus or a lump near the anus. Other symptoms may include pain, itchiness, or discharge from the anus. A change in bowel movements may also occur.

<span class="mw-page-title-main">Cervical intraepithelial neoplasia</span> Medical condition

Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer. More specifically, CIN refers to the potentially precancerous transformation of cells of the cervix.

<span class="mw-page-title-main">HPV vaccine</span> Class of vaccines against human papillomavirus

Human papillomavirus (HPV) vaccines are vaccines that prevent infection by certain types of human papillomavirus (HPV). Available HPV vaccines protect against either two, four, or nine types of HPV. All HPV vaccines protect against at least HPV types 16 and 18, which cause the greatest risk of cervical cancer. It is estimated that HPV vaccines may prevent 70% of cervical cancer, 80% of anal cancer, 60% of vaginal cancer, 40% of vulvar cancer, and show more than 90% effectiveness in preventing HPV-positive oropharyngeal cancers. They also protect against penile cancer. They additionally prevent some genital warts, with the quadrivalent and nonavalent vaccines that protect against HPV types HPV-6 and HPV-11 providing greater protection.

<span class="mw-page-title-main">Ian Frazer</span> Scottish-born Australian immunologist

Ian Hector Frazer is a Scottish-born Australian immunologist, the founding CEO and Director of Research of the Translational Research Institute (Australia). Frazer and Jian Zhou developed and patented the basic technology behind the HPV vaccine against cervical cancer at the University of Queensland. Researchers at the National Cancer Institute, Georgetown University, and University of Rochester also contributed to the further development of the cervical cancer vaccine in parallel.

Cervarix is a vaccine against certain types of cancer-causing human papillomavirus (HPV).

Margaret Anne Stanley, OBE FMedSc, is a British virologist and epithelial biologist. She attended the Universities of London, Bristol, and Adelaide. As of 2018, she is an Emeritus Professor of Epithelial Biology in the Department of Pathology at the University of Cambridge and a Fellow of the Academy of Medical Sciences. She is also an Honorary Fellow of the UK Royal College of Obstetricians and Gynaecologists and an honorary fellow of Christ's College, Cambridge. Stanley is a research scientist in virology focusing on the human papillomavirus (HPV). Her research work has led to new scientific findings on HPV. Additionally, she uses her expertise on HPV to serve on multiple advisory committees and journal editorial boards.

Established in 1993 by Ludwig Cancer Research and McGill University, the Ludwig / McGill Cohort is one of the world's largest longitudinal studies of the natural history of human papillomavirus (HPV) infection and cervical cancer risk.

HspE7 is an investigational therapeutic vaccine candidate being developed by Nventa Biopharmaceuticals for the treatment of precancerous and cancerous lesions caused by the human papillomavirus (HPV). HspE7 uses recombinant DNA technology to covalently fuse a heat shock protein (Hsp) to a target antigen, thereby stimulating cellular immune system responses to specific diseases. HspE7 is a patented construct consisting of the HPV Type 16 E7 protein and heat shock protein 65 (Hsp65) and is currently the only candidate using Hsp technology to target the over 20 million Americans already infected with HPV.

A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. Subunit vaccine can be made from dissembled viral particles in cell culture or recombinant DNA expression, in which case it is a recombinant subunit vaccine.

<span class="mw-page-title-main">Jian Zhou</span> Chinese virologist and cancer researcher

Jian Zhou was a Chinese virologist and cancer researcher, who with fellow researcher Ian Frazer, invented Gardasil and Cervarix, the vaccines for stimulating human immunological resistance to the cervical cancer-inducing human papilloma virus.

Diane Medved Harper is a United States professor in the Department of Family Medicine at the University of Michigan. Her area of expertise is human papillomavirus (HPV) and the diseases associated with it, as well as colposcopy, and she was one of the investigators in the clinical trials of Gardasil and Cervarix, vaccines against HPV.

Human papillomavirus (HPV)-associated oropharyngeal cancer awareness and prevention is a vital concept from a public and community health perspective.

Maria Saveria Campo FRSE, known as Saveria, is an Italian viral oncologist, known for being the first person to demonstrate an effective papillomavirus vaccine. She developed the vaccine alongside her colleague at the University of Bristol, England, Dr. Richard B.S. Roden. She went on to be recognized for her work and was awarded the position of Fellow of the Royal Society of Edinburgh in 2006. She has worked continuously in the field of Oncology up until her retirement.

Kathrin U. Jansen is the former Head of Vaccine Research and Development at Pfizer. She previously led the development of the HPV vaccine (Gardasil) and newer versions of the pneumococcal conjugate vaccine (Prevnar), and is working with BioNTech to create a COVID-19 vaccine using mRNA that was approved for Emergency Use Authorization in the United States on December 11, 2020.

<span class="mw-page-title-main">HPV Prevention and Control Board</span>

The HPV Prevention and Control Board, founded in 2015, is an independent group of international experts supported by unrestricted grants from the pharmaceutical industry that bring together key professionals, groups and government officials to deal with issues related to screening and prevention programmes for human papillomavirus (HPV) infection, the persistence of which may lead to cervical cancer, the second most common cancer in women living in low-resource settings. The Board focusses on preventing cervical cancer in these countries by promoting the sharing of information on cervical screening and HPV vaccination, which by 2014 had reached only around 3% of eligible girls in low income countries.

References

  1. ↑ "Human papillomavirus vaccine Use During Pregnancy". Drugs.com. 11 February 2019. Archived from the original on 5 April 2020. Retrieved 3 April 2020.
  2. ↑ "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  3. ↑ "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada . 4 May 2016. Retrieved 7 April 2024.
  4. 1 2 "Gardasil 9 suspension for injection - Summary of Product Characteristics (SmPC)". (emc). 24 January 2020. Archived from the original on 6 April 2020. Retrieved 3 April 2020.
  5. 1 2 "Gardasil- human papillomavirus quadrivalent- types 6, 11, 16, and 18 vaccine, recombinant injection, suspension". DailyMed. 2 December 2020. Archived from the original on 21 April 2022. Retrieved 31 March 2022.
  6. 1 2 3 4 5 6 7 8 9 "Gardasil 9- human papillomavirus 9-valent vaccine, recombinant injection, suspension". DailyMed. 20 August 2021. Archived from the original on 5 April 2020. Retrieved 31 March 2022.
  7. 1 2 "Silgard EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 6 April 2020. Retrieved 3 April 2020.
  8. 1 2 3 4 5 6 "Gardasil 9 EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 6 April 2020. Retrieved 3 April 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  9. 1 2 3 "Gardasil EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 11 June 2022. Retrieved 6 July 2022.
  10. ↑ "Silgard European Public Assessment Report". European Medicines Agency. 25 September 2009. Archived from the original on 25 December 2008. Retrieved 5 December 2009.
  11. ↑ Waknine Y (2 October 2006). "International Approvals: Singulair and Gardasil/Silgard". Medscape Today. Archived from the original on 20 May 2013. Retrieved 18 December 2008.
  12. ↑ Richwine L (20 August 2009). "U.S. health officials back safety of Merck vaccine". Reuters. Archived from the original on 27 August 2009. Retrieved 12 November 2009.
  13. ↑ Gizzo S, Noventa M, Nardelli GB (September 2013). "Gardasil administration to hr-HPV-positive women and their partners". Trends in Pharmacological Sciences. 34 (9): 479–80. doi:10.1016/j.tips.2013.07.001. PMID   23896431.
  14. ↑ "Genital HPV Infection - Fact Sheet". www.cdc.gov. U.S. Centers for Disease Control and Prevention (CDC). Archived from the original on 11 September 2012. Retrieved 18 April 2020.
  15. 1 2 3 Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER, et al. (Advisory Committee on Immunization Practices (ACIP), Centers for Disease Control Prevention (CDC)) (March 2007). "Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP)" (PDF). MMWR. Recommendations and Reports. 56 (RR-2): 1–24. PMID   17380109. Archived (PDF) from the original on 24 September 2015.
  16. 1 2 Centers for Disease Control Prevention (CDC) (May 2010). "FDA licensure of quadrivalent human papillomavirus vaccine (HPV4, Gardasil) for use in males and guidance from the Advisory Committee on Immunization Practices (ACIP)" (PDF). MMWR. Morbidity and Mortality Weekly Report. 59 (20): 630–2. PMID   20508594. Archived (PDF) from the original on 24 September 2015.
  17. 1 2 Lowy DR, Schiller JT (May 2006). "Prophylactic human papillomavirus vaccines". The Journal of Clinical Investigation. 116 (5): 1167–73. doi: 10.1172/JCI28607 . PMC   1451224 . PMID   16670757.
  18. 1 2 Muñoz N, Bosch FX, Castellsagué X, Díaz M, de Sanjose S, Hammouda D, et al. (August 2004). "Against which human papillomavirus types shall we vaccinate and screen? The international perspective". International Journal of Cancer. 111 (2): 278–85. doi: 10.1002/ijc.20244 . PMID   15197783.
  19. 1 2 3 Gao G, Smith DI (2016). "Human Papillomavirus and the Development of Different Cancers". Cytogenetic and Genome Research. 150 (3–4): 185–193. doi: 10.1159/000458166 . PMID   28245440. Archived from the original on 17 July 2020. Retrieved 19 April 2020.
  20. 1 2 "FDA Approves Expanded Uses for Gardasil to Include Preventing Certain Vulvar and Vaginal Cancers" (Press release). U.S. Food and Drug Administration (FDA). 12 September 2008. Archived from the original on 6 March 2010. Retrieved 11 November 2009.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  21. 1 2 3 "Human papillomavirus vaccines: WHO position paper, May 2017". Weekly Epidemiological Record. 92 (19): 241–268. May 2017. hdl:10665/255353. PMID   28530369.
  22. 1 2 3 4 5 Anjum F, Zohaib J (4 December 2020). "Oropharyngeal Squamous Cell Carcinoma". Definitions (Updated ed.). Treasure Island (FL): StatPearls Publishing. doi:10.32388/G6TG1L. PMID   33085415. S2CID   229252540. Bookshelf ID: NBK563268. Archived from the original on 11 June 2021. Retrieved 7 February 2021– via NCBI.{{cite book}}: |work= ignored (help)
  23. 1 2 3 "Human Papillomavirus (HPV) Vaccines". National Cancer Institute. Archived from the original on 21 June 2008. Retrieved 18 April 2020.
  24. ↑ "Gardasil". U.S. Food and Drug Administration. 15 June 2017. Archived from the original on 22 July 2017. Retrieved 3 April 2020.
  25. ↑ "FDA Licenses New Vaccine for Prevention of Cervical Cancer and Other Diseases in Females Caused by Human Papillomavirus" (Press release). U.S. Food and Drug Administration (FDA). 8 June 2006. Archived from the original on 19 October 2009. Retrieved 13 November 2009.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  26. ↑ "Gardasil" . Britannica Academic. April 2018. Archived from the original on 13 April 2020. Retrieved 7 May 2019.
  27. ↑ Moro PL, Zheteyeva Y, Lewis P, Shi J, Yue X, Museru OI, et al. (January 2015). "Safety of quadrivalent human papillomavirus vaccine (Gardasil) in pregnancy: adverse events among non-manufacturer reports in the Vaccine Adverse Event Reporting System, 2006-2013". Vaccine. 33 (4): 519–22. doi:10.1016/j.vaccine.2014.11.047. PMC   6524774 . PMID   25500173. Archived from the original on 13 April 2020. Retrieved 7 May 2019.
  28. 1 2 "Gardasil Vaccine Safety". U.S. Food and Drug Administration (FDA). 20 August 2009. Archived from the original on 3 May 2019. Retrieved 21 October 2019.
  29. ↑ Haupt RM, Sings HL (November 2011). "The efficacy and safety of the quadrivalent human papillomavirus 6/11/16/18 vaccine gardasil". The Journal of Adolescent Health. 49 (5): 467–75. doi:10.1016/j.jadohealth.2011.07.003. PMID   22018560.
  30. ↑ "Gardasil 9". U.S. Food and Drug Administration (FDA). 10 October 2018. Archived from the original on 23 April 2019. Retrieved 3 April 2020.
  31. ↑ "FDA approves Gardasil 9 for prevention of certain cancers caused by five additional types of HPV" (press release). U.S. Food and Drug Administration (FDA). 10 December 2014. Archived from the original on 10 January 2015. Retrieved 28 February 2015.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  32. 1 2 "FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old" (Press release). U.S. Food and Drug Administration (FDA). 5 October 2018. Archived from the original on 14 October 2019. Retrieved 14 October 2018.
  33. ↑ "14. Vaccines". British National Formulary (BNF) (82 ed.). London: BMJ Group and the Pharmaceutical Press. September 2021 – March 2022. pp. 1362–1390. ISBN   978-0-85711-413-6.
  34. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 "Gardasil 9". U.S. Food and Drug Administration (FDA). 12 June 2020. Archived from the original on 15 October 2019. Retrieved 15 June 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  35. ↑ Wang JW, Roden RB (February 2013). "Virus-like particles for the prevention of human papillomavirus-associated malignancies". Expert Review of Vaccines. 12 (2): 129–41. doi:10.1586/erv.12.151. PMC   3835148 . PMID   23414405.
  36. ↑ "Humanitas Papiloma Virus". Archived from the original on 28 February 2017. Retrieved 26 February 2018.
  37. ↑ "FDA: Gardasil approved to prevent anal cancer" (Press release). U.S. Food and Drug Administration (FDA). 22 December 2010. Archived from the original on 18 December 2014. Retrieved 4 January 2011.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  38. ↑ Goon PK, Stanley MA, Ebmeyer J, Steinsträsser L, Upile T, Jerjes W, et al. (October 2009). "HPV & head and neck cancer: a descriptive update". Head & Neck Oncology. 1 (1): 36. doi: 10.1186/1758-3284-1-36 . PMC   2770444 . PMID   19828033.
  39. ↑ Vousden KH (1994). Cell transformation by human papillomaviruses. New York: Press Syndicate of the University of Cambridge. pp. 27–46. ISBN   9780521454728.{{cite book}}: |work= ignored (help)
  40. ↑ Masters C (11 May 2007). "Oral Sex Can Add to HPV Cancer Risk". Time . Archived from the original on 4 April 2020.
  41. ↑ "FDA Approves Merck's Gardasil 9 for the Prevention of Certain HPV-Related Head and Neck Cancers". Merck (Press release). 12 June 2020. Archived from the original on 30 May 2021. Retrieved 15 June 2020.
  42. ↑ "Gardasil Supplement Accelerated Approval" (PDF). U.S. Food and Drug Administration (FDA). 12 June 2020. Archived from the original on 16 June 2020. Retrieved 15 June 2020.
  43. ↑ Lei J, Ploner A, Elfström KM, Wang J, Roth A, Fang F, et al. (October 2020). "HPV Vaccination and the Risk of Invasive Cervical Cancer". The New England Journal of Medicine. 383 (14): 1340–1348. doi: 10.1056/NEJMoa1917338 . PMID   32997908.
  44. ↑ Centers for Disease Control Prevention (May 2010). "FDA licensure of bivalent human papillomavirus vaccine (HPV2, Cervarix) for use in females and updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices (ACIP)" (PDF). MMWR. Morbidity and Mortality Weekly Report. 59 (20): 626–9. PMID   20508593. Archived (PDF) from the original on 24 September 2015. Retrieved 9 September 2017.
  45. 1 2 "Human Papillomavirus (HPV) Vaccines". National Cancer Institute (NCI). 9 September 2019. Archived from the original on 4 April 2020. Retrieved 3 April 2020.
  46. ↑ Schieszer J (November 2007). "HPV Vaccine Protects Against 10 "Other" Strains". Internal Medicine World Report. Archived from the original on 4 December 2008.
  47. ↑ World Health Organization (April 2014). "Summary of the SAGE April 2014 meeting". Archived from the original on 31 July 2015. Retrieved 2 June 2015.
  48. ↑ "CDC recommends only two HPV shots for younger adolescents" (Press release). U.S. Centers for Disease Control and Prevention (CDC). 19 October 2016. Archived from the original on 23 March 2017. Retrieved 7 October 2017.
  49. ↑ Giuliano AR, Palefsky JM, Goldstone S, Moreira ED, Penny ME, Aranda C, et al. (February 2011). "Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males". The New England Journal of Medicine. 364 (5): 401–11. doi: 10.1056/NEJMoa0909537 . PMC   3495065 . PMID   21288094.
  50. ↑ Carter M (7 February 2011). "Gardasil safe and effective in young men". aidsmap.com. NAM aidsmap. Archived from the original on 24 January 2022. Retrieved 24 January 2022.
  51. ↑ "Gay men seeking HPV vaccine". Cancer Research UK . 23 February 2007. Archived from the original on 24 March 2010. Retrieved 12 November 2009.
  52. ↑ "FDA Approves New Indication for Gardasil to Prevent Genital Warts in Men and Boys" (Press release). U.S. Food and Drug Administration (FDA). 16 October 2009. Archived from the original on 24 October 2009. Retrieved 12 November 2009.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  53. ↑ "October 16, 2009 Approval Letter – Gardasil". U.S. Food and Drug Administration (FDA). 16 October 2009. Archived from the original on 24 October 2009. Retrieved 12 November 2009.
  54. ↑ "FDA licensure of 9-valent human papillomavirus vaccine to include males aged 16–26 years" (PDF). U.S. Centers for Disease Control and Prevention (CDC). 14 December 2015. Archived (PDF) from the original on 30 January 2017. Retrieved 10 October 2016.
  55. ↑ "Provider Information: Gardasil 9 VIS" (PDF). U.S. Centers for Disease Control and Prevention (CDC). December 2015. Archived (PDF) from the original on 11 February 2017. Retrieved 10 October 2016.
  56. ↑ "Highlights of Prescribing InformationI: Gardasil 9" (PDF). U.S. Food and Drug Administration (FDA). 14 December 2015. Archived (PDF) from the original on 10 October 2016. Retrieved 10 October 2016.
  57. ↑ Roberts M (23 February 2007). "Gay men seek 'female cancer' jab". BBC News Online . Archived from the original on 30 January 2009. Retrieved 12 November 2009.
  58. ↑ D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. (May 2007). "Case-control study of human papillomavirus and oropharyngeal cancer". The New England Journal of Medicine. 356 (19): 1944–56. doi: 10.1056/NEJMoa065497 . PMID   17494927.
  59. ↑ Bernard EJ (29 August 2005). "HAART is not reducing risk of anal cancer in gay men". AIDSmap. Archived from the original on 19 June 2006. Retrieved 8 June 2006.
  60. ↑ "Gardasil suspension for injection - Summary of Product Characteristics (SmPC)". (emc). 7 May 2019. Archived from the original on 4 April 2020. Retrieved 3 April 2020.
  61. ↑ McNeil Jr DJ (31 March 2014). "Expansion in Use of Cancer Vaccine". The New York Times . Archived from the original on 6 February 2016. Retrieved 20 December 2019.
  62. 1 2 3 "HPV Vaccine Information For Young Women". U.S. Centers for Disease Control and Prevention (CDC). Archived from the original on 28 June 2009. Retrieved 14 June 2009.
  63. ↑ Stobbe M (9 February 2009). "Cervical cancer shots are gaining reputation as painful". ABC News . Associated Press. Archived from the original on 12 November 2020. Retrieved 4 April 2020.
  64. ↑ Fagan A (10 July 2008). "Merck, FDA expand Gardasil warnings". The Washington Times . Archived from the original on 17 July 2008.
  65. 1 2 3 Rosenthal E (19 August 2008). "Drug Makers' Push Leads to Cancer Vaccines' Fast Rise". The New York Times . Archived from the original on 9 April 2009. Retrieved 20 August 2008.
  66. 1 2 "Information from FDA and CDC on Gardasil and its Safety (Archived)". U.S. Centers for Disease Control and Prevention (CDC). 22 July 2008. Archived from the original on 2 September 2013. Retrieved 9 September 2017.
  67. ↑ "Reports of Health Concerns Following HPV Vaccination". U.S. Centers for Disease Control and Prevention (CDC). 26 October 2010. Archived from the original on 17 September 2013.
  68. 1 2 Slade BA, Leidel L, Vellozzi C, Woo EJ, Hua W, Sutherland A, et al. (August 2009). "Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine". JAMA. 302 (7): 750–7. doi:10.1001/jama.2009.1201. PMID   19690307.
  69. ↑ "HPV Vaccine – Questions & Answers for the Public". 18 July 2008. Archived from the original on 6 March 2008. Retrieved 22 August 2008.
  70. ↑ "Guillain–Barré Syndrome Fact Sheet". National Institute of Neurological Disorders and Stroke (NINDS). 6 May 2010. Archived from the original on 5 August 2016.
  71. ↑ Chustecka Z (18 August 2009). "HPV Vaccine: Debate Over Benefits, Marketing, and New Adverse Event Data". Medscape Today. Archived from the original on 14 November 2010. Retrieved 27 August 2009.
  72. ↑ Castillo R (10 February 2009). "Spain halts batch of Merck's Gardasil". Reuters. Archived from the original on 13 February 2009. Retrieved 10 February 2009.
  73. ↑ Harper DM, DeMars LR (July 2017). "HPV vaccines - A review of the first decade". Gynecologic Oncology. 146 (1): 196–204. doi: 10.1016/j.ygyno.2017.04.004 . PMID   28442134. Archived from the original on 11 December 2021. Retrieved 19 April 2020.
  74. ↑ "Gardasil Product Monograph" (PDF). Merck Canada Inc. Archived (PDF) from the original on 4 April 2020. Retrieved 3 April 2020.
  75. 1 2 3 Jenco M (9 August 2018). "Cervical cancer declines follow HPV vaccine introduction". AAP News. Archived from the original on 14 April 2021. Retrieved 2 October 2018.
  76. ↑ Cohen J (April 2005). "Public health. High hopes and dilemmas for a cervical cancer vaccine". Science. 308 (5722): 618–21. doi:10.1126/science.308.5722.618. PMID   15860602. S2CID   31712160.
  77. ↑ "Cervical Cancer: Statistics". January 2018. Archived from the original on 27 September 2021. Retrieved 2 October 2018.
  78. 1 2 3 "FDA approves first vaccine for cervical cancer". NBC News. Associated Press. 16 June 2006. Archived from the original on 6 August 2020. Retrieved 8 June 2006.
  79. ↑ "SEER Stat Fact Sheets: Cervix Uteri". National Cancer Institute . Archived from the original on 6 July 2014. Retrieved 30 March 2007.
  80. ↑ "Health Blue Book". Archived from the original on 11 December 2021. Retrieved 15 August 2012.
  81. ↑ Stanley M (November 2007). "Prevention strategies against the human papillomavirus: the effectiveness of vaccination". Gynecologic Oncology. 107 (2 Suppl 1): S19-23. doi:10.1016/j.ygyno.2007.07.068. PMID   17938013.
  82. ↑ Pallecaros A, Vonau B (December 2007). "Human papilloma virus vaccine--more than a vaccine". Current Opinion in Obstetrics & Gynecology. 19 (6): 541–6. doi:10.1097/GCO.0b013e3282f1a91b. PMID   18007131. S2CID   2309744.
  83. ↑ Morris SK, Nguyen CK (2008). "The human papillomavirus vaccine in Canada". Canadian Journal of Public Health. 99 (2): 114–6. doi:10.1007/BF03405456. PMC   6975757 . PMID   18457284.
  84. ↑ Steben M (March 2008). "Rebuttal: Do you approve of spending $300 million on HPV vaccination? Yes". Canadian Family Physician. 54 (3): 342, 344. PMC   2278341 . PMID   18337521.
  85. ↑ Rothman SM, Rothman DJ (August 2009). "Marketing HPV vaccine: implications for adolescent health and medical professionalism". JAMA. 302 (7): 781–6. doi:10.1001/jama.2009.1179. PMID   19690311.
  86. ↑ Haelle T (23 February 2016). "HPV Infection Rates Plummet In Young Women Due To Vaccine". Forbes. Archived from the original on 26 February 2016. Retrieved 23 February 2016.
  87. ↑ McNeil C (April 2006). "Who invented the VLP cervical cancer vaccines?". Journal of the National Cancer Institute. 98 (7): 433. doi: 10.1093/jnci/djj144 . PMID   16595773.
  88. ↑ Inglis S, Shaw A, Koenig S (31 August 2006). "HPV vaccines: commercial research & development". Vaccine. 24 Suppl 3: S3/99-105. doi:10.1016/j.vaccine.2006.05.119. PMID   16950023.
  89. ↑ "FDA Approves Merck's HPV Vaccine, GARDASIL 9, to Prevent Cancers and Other Diseases Caused by Nine HPV types – Including Types that Cause About 90% of Cervical Cancer Cases". Merck (Press release). 11 December 2014. Archived from the original on 6 July 2022. Retrieved 6 July 2022.
  90. ↑ "Gardasil 9". U.S. Food and Drug Administration (FDA). 21 February 2020. STN: 125508. Archived from the original on 15 October 2019. Retrieved 4 April 2020.
  91. 1 2 Fortson D (11 June 2006). "Moral majority take on GSK and Merck over cancer drugs". The Independent . Archived from the original on 14 June 2006. Retrieved 12 June 2006.
  92. ↑ Barillas M (14 September 2006). "Gardasil vaccine touted in Michigan". Spero News. Archived from the original on 14 November 2006. Retrieved 26 January 2007.
  93. ↑ Gaul M (2007). "Gardasil: What Parents should know about the new HPV vaccine" (PDF). Family Research Council. Archived (PDF) from the original on 13 July 2021. Retrieved 13 September 2011.
  94. ↑ Bednarczyk RA, Davis R, Ault K, Orenstein W, Omer SB (November 2012). "Sexual activity-related outcomes after human papillomavirus vaccination of 11- to 12-year-olds". Pediatrics. 130 (5): 798–805. doi: 10.1542/peds.2012-1516 . PMID   23071201.
  95. ↑ Pollack A, Saul S (21 February 2007). "Merck to halt lobbying for vaccine for girls". The New York Times . Archived from the original on 12 April 2018. Retrieved 4 July 2018.
  96. ↑ Houppert K (26 March 2007). "Who's Afraid of Gardasil?". The Nation . Retrieved 11 November 2009.
  97. ↑ Gabriel T, Grady D (13 September 2011). "In Republican Race, a Heated Battle Over the HPV Vaccine". The New York Times . Archived from the original on 14 September 2011. Retrieved 14 September 2011.
  98. ↑ "Cervix vaccine issues trigger health notice". Japan Times. 16 June 2013. Archived from the original on 3 December 2013. Retrieved 9 July 2013.
  99. ↑ "Health ministry withdraws recommendation for cervical cancer vaccine". The Asahi Shimbun. 15 June 2013. Archived from the original on 19 June 2013. Retrieved 9 July 2013.
  100. 1 2 Hanley SJ, Yoshioka E, Ito Y, Kishi R (June 2015). "HPV vaccination crisis in Japan". Lancet. 385 (9987): 2571. doi: 10.1016/S0140-6736(15)61152-7 . PMID   26122153.
  101. ↑ Haruyama R, Obara H, Fujita N (February 2022). "Japan resumes active recommendations of HPV vaccine after 8·5 years of suspension". Lancet Oncology. 23 (2): 197–198. doi:10.1016/S1470-2045(22)00002-X. PMID   35114115. S2CID   246455402.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.